Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
Department of Orthopaedics, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7423-7431. doi: 10.3892/mmr.2017.7577. Epub 2017 Sep 21.
Osteosarcoma is a common and highly malignant tumour in children and teenagers that is characterized by drug resistance and high metastatic potential. Patients often develop pulmonary metastasis and have a low survival rate. However, the mechanistic basis for pulmonary metastasis remains unclear. To identify key gene and pathways associated with pulmonary metastasis of osteosarcoma, the authors downloaded the gene expression dataset GSE85537 and obtained the differentially expressed genes (DEGs) by analyzing high‑throughput gene expression in primary tumours and lung metastases. Subsequently, the authors performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses and a protein‑protein interaction (PPI) network was constructed and analyzed by Cytoscape software. In total, 2,493 genes were identified as DEGs. Of these, 485 genes (19.45%) were upregulated, and the remaining 2,008 genes (80.55%) were downregulated. The authors identified the predominant GO categories and KEGG pathways that were significantly over‑represented in the metastatic OS samples compared with the non‑metastatic OS samples. A PPI network was constructed, and the results indicated that ALB, EGFR, INS, IL6, CDH1, FYN, ERBB2, IL8, CXCL12 and RAC2 were the top 10 core genes. The enrichment analyses of the genes involved in the top three significant modules demonstrated that the DEGs were principally related to neuroactive ligand‑receptor interaction, the Rap1 signaling pathway, and protein digestion and absorption. Together, these data elucidated the molecular mechanisms of OS patients with pulmonary metastasis and provide potential therapeutic targets. However, further experimental studies are needed to confirm these results.
骨肉瘤是儿童和青少年中常见且高度恶性的肿瘤,其特征是耐药性和高转移潜能。患者常发生肺转移,生存率低。然而,肺转移的机制基础仍不清楚。为了鉴定与骨肉瘤肺转移相关的关键基因和通路,作者下载了基因表达数据集 GSE85537,并通过分析原发肿瘤和肺转移中的高通量基因表达获得差异表达基因(DEGs)。随后,作者进行了基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,并使用 Cytoscape 软件构建和分析了蛋白质-蛋白质相互作用(PPI)网络。共鉴定出 2493 个 DEGs。其中,485 个基因(19.45%)上调,其余 2008 个基因(80.55%)下调。作者确定了与非转移性 OS 样本相比,转移性 OS 样本中显著过表达的主要 GO 类别和 KEGG 通路。构建了 PPI 网络,结果表明 ALB、EGFR、INS、IL6、CDH1、FYN、ERBB2、IL8、CXCL12 和 RAC2 是前 10 个核心基因。参与前三个显著模块的基因的富集分析表明,DEGs 主要与神经活性配体-受体相互作用、Rap1 信号通路和蛋白质消化吸收有关。综上所述,这些数据阐明了具有肺转移的骨肉瘤患者的分子机制,并提供了潜在的治疗靶点。然而,需要进一步的实验研究来验证这些结果。